National Cancer Institute

at the National Institutes of Health

Genetics of Breast and Gynecologic Cancers (PDQ®)

Psychosocial Issues in Inherited Breast and Ovarian Cancer Syndromes

Introduction

Psychosocial research in the context of cancer genetic testing helps to define
psychological outcomes, interpersonal and familial effects, and cultural and
community responses. This type of research also identifies behavioral factors that encourage or
impede screening and other health behaviors. It can enhance decision-making
about risk-reduction interventions, evaluate psychosocial interventions to
reduce distress and/or other negative sequelae related to risk notification and
genetic testing, provide data to help resolve ethical concerns, and predict the
interest in testing of various groups.

Research in these areas is limited by few randomized controlled trials, and many
reports are based on uncontrolled studies of selected high-risk populations.
Research is likely to expand considerably with access to larger populations of
at-risk individuals.

There have been a number of descriptions of cancer genetics programs that provide genetic susceptibility testing.[1-9] The development of such programs was encouraged by federal funding of multidisciplinary research programs that offered intensive genetic counseling for hereditary cancer syndromes, psychological assessment and back-up, and physician involvement.[10]

Uptake of Genetic Counseling and Genetic Testing

Degree of uptake of genetic counseling and genetic testing

Comparison of uptake rates across studies is challenging because of differences in methodologies, including the sampling strategy used, the recruitment setting, and testing through a research protocol with high-risk cohorts or kindreds. In a systematic review of 40 studies conducted before 2002 that had assessed genetic testing utilization, uptake rates varied widely and ranged from 25% to 96%, with an average uptake rate of 59%.[11] Results of multivariate analysis found that BRCA1/BRCA2 genetic testing uptake was associated with having a personal or family history of breast or ovarian cancer, and with methodological features of the studies, including sampling strategies, recruitment settings, and how studies defined actual uptake versus the intention to have testing.

Other factors have been positively correlated with uptake of BRCA1/BRCA2 genetic testing, although these findings are not consistent across all studies. Psychological factors that have been positively correlated with testing uptake include greater cancer-specific distress and greater perceived risk of developing breast or ovarian cancer. Having more cancer-affected relatives also has been correlated with greater testing uptake.

Table 13 summarizes the uptake of genetic testing in clinical and research cohorts in the United States.

Race/ethnicity. African American women were less likely to be tested than were white women.

Sample obtained from a clinical database. Testing was offered free of charge when it was not covered by insurance. This effect for time of diagnosis was significant in the African American, but not white, subgroup.

African American women: 77/132 (58%) underwent GT

Recent diagnosis. African American women who were recently diagnosed were more likely to be tested.

Personal history of breast cancer. Having a personal history was associated with 3 times greater odds of being tested.

Insurance coverage for testing was available for 91.1% (175/213) of patients. Of those who had coverage for GT, 51.4% underwent testing and 48.6% did not. Of those without coverage, 41.2% had GT and 58.9% did not.

102/213 (48%) declined GT

Higher level of education. Those with a high school education or less had one-third the odds of being tested, compared with those with at least some college.

Race/ethnicity. Women of Jewish ethnicity were 3 times more likely to be tested than were non-Jewish white women. African American and Hispanic women were significantly less likely to receive testing than were non-Jewish white women.

Sample obtained from a national database of commercially insured individuals.

Jewish women:
18/32 (56%) underwent GT

Home location. Women living in the south were more likely to be tested than were women living in the northeast.

African American women:
10/82 (12%) underwent GT

Insurance type. Women with point-of-service plans were more likely to be tested than were women with HMO plans.

Recent diagnosis. Women diagnosed in 2007 were 3.8 times more likely to be tested than were women diagnosed in 2004.

Several studies conducted in non-U.S. settings have examined the uptake of genetic testing.[17-21] In studies examining the uptake of testing among at-risk relatives of BRCA1/BRCA2 mutation carriers, uptake rates have averaged below 50% (range, 36%–48%), with higher uptake reported among female relatives than in male relatives. Other factors associated with higher uptake of testing were not consistently reported among studies but have most commonly included being a parent and wanting to learn information about a child’s risk.

Factors influencing uptake of genetic counseling and genetic testing

In reviews that have examined the cumulative evidence concerning the predictors of uptake of BRCA1/BRCA2 genetic testing, important predictors of testing uptake include older age, Ashkenazi Jewish (AJ) heritage, unmarried status, a personal history of breast cancer, and a family history of breast cancer. Studies recruiting participants in hospital settings had significantly higher recruitment rates than did studies recruiting participants in community settings. Studies that required an immediate decision to test, rather than allowing delayed decision making, tended to report higher uptake rates.[11] However, there is evidence that women diagnosed with breast cancer are equally satisfied with genetic counseling (including information received and strength and timing of physician recommendations for counseling), whether they received genetic counseling before or after their definitive surgery for breast cancer.[22] Another review [23] found that uptake of genetic testing for BRCA1/2 mutations was related to psychological factors (e.g., anxiety about breast cancer and perceived risk of breast cancer) and demographic and medical factors (e.g., history of breast cancer or ovarian cancer, presence of children, and higher number of affected first-degree relatives). Family members with a known BRCA1/2 mutation were more likely to pursue testing; those with more extensive knowledge of BRCA1/2 testing, heightened risk perceptions, beliefs that mammography would promote health benefit, and high intentions to undergo testing were more likely to follow through with testing.[24]

In a review of racial/ethnic differences that affect uptake of BRCA1/2 testing, intention to undergo genetic testing in African American women was related to having at least one first-degree relative with breast cancer or ovarian cancer, higher perceived risk of being a carrier, and less anticipatory guilt about the possibility of being a gene carrier.[25]

Reasons cited for following through with testing included a desire to learn about a child's risk, to feel relief from uncertainty, to inform screening or prophylactic surgery decisions, and to inform important life decisions such as marriage and childbearing.[24,26] Among African American women, the most important reason for testing included motivation to help other relatives decide on genetic testing.[25]

Physician recommendation may be another motivator for testing. In a retrospective study of 335 women considering genetic testing, 77% reported that they wanted the opinion of a genetics physician about whether they should be tested, and 49% wanted the opinion of their primary care provider.[27] However, there is some evidence of referral bias favoring those with a maternal family history of breast cancer or ovarian cancer. In a Canadian retrospective review of 315 patients, those with a maternal family history of breast cancer or ovarian cancer were 4.9 times (95% confidence interval, 3.6–6.7) more likely to be referred for a cancer genetics consultation by their physician than were those with a paternal family history (P < .001).[28] Studies have found that physicians may not adequately assess paternal family history [29] or may underestimate the significance of a paternal family history for genetic risk.[29-31]

Insurance coverage

In May 2011, a case study examined coverage for BRCA1/2 testing using National Comprehensive Cancer Network (NCCN) clinical guidelines. The online databases included data from large private insurers (eight payers, including Aetna, Cigna, Humana, and United HealthCare) and public insurance policies, including Medicare (Washington state) and four Medicaid policies (Arizona, California, Illinois, and New York). Overall, more consistent policies were available for private than for public payers, indicating better communication of eligibility criteria and transparency of coverage. However, across all types of coverage, including private coverage, the criteria were inconsistent for coverage of genetic counseling services. Of note, the Medicare policies only covered individuals with a history of breast cancer, not those with strong family histories, as outlined by NCCN.[32]

Conducted in 2008, another study examined coverage policies from all third-party payers in Illinois and documented relative consistency in coverage for genetic testing for breast/ovarian cancer and colorectal cancer susceptibility, but much less consistent approaches to coverage for genetic counseling services; for example, several policies would not cover genetic counseling services unless the patient ultimately decided against genetic testing.[33] One example of success in changing coverage plans was initiated by the Michigan Department of Community Health, which used
a cooperative agreement with the Centers for Disease Control and Prevention to raise awareness and provide guidance for an increase in written policies regarding BRCA1/2 testing, increasing utilization from 4 to 11 health plans.[34] As of August 2011, 11 of 24 Michigan health plans had written BRCA1/2 genetic testing policies aligned with U.S. Preventive Services Task Force guidelines. There is evidence that concerns about genetic discrimination are decreasing. A 2007 survey of genetic counselors reported that most (94%) felt the risk of insurance discrimination resulting from genetic testing was low, and that they were confident in U.S. laws to protect against genetic discrimination.[35]

Uptake of genetic counseling and genetic testing in diverse populations

Degree of uptake of genetic counseling and genetic testing in diverse populations

There are limited data on uptake of genetic counseling and testing among nonwhite populations, and further research will be needed to define factors influencing uptake in these populations.[36] The uptake of BRCA testing appears to vary across some racial/ethnic groups. A few studies have compared uptake rates between African American and white women.[14,37] In a case-control study of women who had been seen in a university-based primary care system, African American women with family histories of breast cancer or ovarian cancer were less likely to undergo BRCA1/2 testing than were white women who had similar histories.[37] In another study among breast cancer patients who were counseled about BRCA1/2 risk in a clinical setting, lower uptake was reported among African American women than among white women.[14]

Notably, the racial differences observed in these studies do not appear to be explained by factors related to cost, access to care, risk factors for carrying a BRCA1 or BRCA2 mutation, or differences in psychosocial factors, including risk perceptions, worry, or attitudes toward testing.

Several studies have examined uptake or “acceptance” of BRCA testing among African Americans enrolled in genetic research programs. Among study enrollees from an African American kindred in Utah, 83% underwent BRCA1 testing.[38] Age, perceived risk of being a carrier, and more extensive cancer knowledge predicted testing acceptance. Another study that recruited African American women through physician and community referrals reported a BRCA1/2 testing acceptance rate of 22%.[39] Predictors of test acceptance included having a higher probability of having a mutation, being married, and being less certain about one’s cancer risk. Finally, a third study that recruited at-risk African American women from an urban cancer screening clinic found that acceptors of BRCA testing were more knowledgeable about breast cancer genetics and perceived fewer barriers to testing, including negative emotional reactions, stigmatization concerns, and family-related guilt.[40] While these are independent predictors of genetic testing uptake, they do not explain the disparities in testing uptake across different ethnic groups. What may explain these differences are several attitudes and beliefs held about testing by individuals from diverse populations.

Recent work examining attitudes toward breast cancer genetic testing in African American and Latino populations indicates limited knowledge and awareness about testing but a generally receptive view once they are informed; in comparison with whites, African American and Latino populations have relatively more concerns about testing.

For example, in a qualitative focus group study with 51 Latino individuals unselected for risk status, important findings included the fact that participants were highly interested in genetic testing for inherited cancer susceptibility, despite very limited knowledge about genetics. One important barrier involved secrecy or embarrassment about family discussions of cancer and genetics, which could be addressed in intervention strategies.[41] Similarly, a telephone survey of 314 patients, 50% of whom were African American, from an inner-city network of Pittsburgh, Pennsylvania, health centers found that most participants (57%) (both African Americans and whites) felt that genetic testing to evaluate disease risk was a good idea; however, more African Americans than whites thought that genetic testing would lead to racial discrimination (37% vs. 22%, respectively) and that genetics research was unethical and tampered with nature (20% vs. 11%, respectively).[42] Finally, in a study of 222 women in Savannah, Georgia, where most had neither a personal history (70%) nor a family history (60%) of breast cancer, African American women (who comprised 26% of the sample) were less likely to be aware of breast cancer genes and genetic testing. Awareness was also related to higher income, higher education level, and having a family breast cancer history. However, 74% of the entire sample expressed willingness to be tested for breast cancer susceptibility.[43]

In a sample of 146 African American women meeting criteria for BRCA1/2 mutation testing, women born outside the United States reported higher levels of anticipated negative emotional reactions (e.g., fear, hopelessness, and lack of confidence that they could emotionally handle testing). Higher levels of breast cancer–specific distress were associated with anticipated negative emotional reactions, confidentiality concerns, and anticipated guilt regarding the family impact of breast cancer genetic testing.[44] A future orientation (e.g., "I often think about how my actions today will affect my health when I am older") was associated with overall perceived benefits of breast cancer genetic testing in this population (n = 140); however, future orientation was also found to be positively associated with family-related cons of testing, including family guilt and worry regarding the impact of testing on the family.[45]

Factors associated with declining genetic counseling and testing

There is evidence that primary reasons for declining testing involves being childless, which reduces any family motivations for testing; and concerns about the negative ramifications of testing, including difficulty retaining insurance or concerns about personal health.

Limited data are available about the characteristics of at-risk individuals who decline to be tested or have never been tested. It is difficult to access samples of test decliners because they may be reluctant to participate in research studies. Studies of genetic testing uptake are difficult to compare because people may decline at different points and with different amounts of pretest education and counseling. One study found that 43% of affected and unaffected individuals from hereditary breast/ovarian cancer families who completed a baseline interview regarding testing declined to be tested. Most individuals who declined testing chose not to participate in educational sessions. Decliners were more likely to be male and be unmarried, and have fewer relatives with breast cancer. Decliners who had high levels of cancer-related stress had higher levels of depression. Decliners lost to follow-up were significantly more likely to be affected with cancer.[46]

Another study looked at a small number (n = 13) of women decliners who carried a 25% to 50% probability of harboring a BRCA mutation; these nontested women were more likely to be childless and to have higher levels of education. This study showed that most women decided not to undergo the test after serious deliberation about the risks and benefits. Satisfaction with frequent surveillance was given as one reason for nontesting by most of these women.[47] Other reasons for declining included having no children and becoming acquainted with breast/ovarian cancer in the family relatively early in their lives.[46,47]

A third study evaluated characteristics of 34 individuals who declined BRCA1/2 testing in a large multicenter study in the United Kingdom. Decliners were younger than a national sample of test acceptors, and female decliners had lower mean scores on a measure of cancer worry. Although 78% of test decliners/deferrers felt that their health was at risk, they reported that learning about their BRCA1/2 mutation status would cause them to worry about the following:

Their children's health (76%).

Their life insurance (60%).

Their own health (56%).

Loss of their job (5%).

Receiving less screening if they did not carry a BRCA1/2 mutation (62%).

Apprehension about the impact of the test result was a more important factor in the decision to decline testing than were concrete burdens such as time required to travel to a genetics clinic and time spent away from work, family, and social obligations.[48] In 15% (n = 31) of individuals from 13 hereditary breast and ovarian cancer families who underwent genetic education and counseling and declined testing for a documented mutation in the family, positive changes in family relationships were reported—specifically, greater expressiveness and cohesion—compared with those who pursued testing.[49]

Genetic counseling and testing in children

Testing for BRCA1/2 mutations has been almost universally limited to adults older than 18
years. The risks of testing children for adult-onset disorders such as breast
and ovarian cancers, as inferred from developmental data on children’s medical
understanding and ability to provide informed consent, have been outlined in
several reports.[50-53]

Studies suggest that persons who have undergone BRCA1/2 genetic testing or who are adult offspring of persons who have had testing are generally not in favor of testing minors.[54,55] Although the data are limited, research suggests that males, mutation noncarriers, and those whose mothers did not have personal histories of breast cancer may be more likely to favor genetic testing in minors in general.[54] Of those who had minor children at the time the study was conducted, only 17% stated a preference for having their own children tested. Concerns regarding testing of minors included psychological risks and insufficient maturity. Potential benefits included the ability to influence health behaviors.[55]

No data exist on the testing of children for
BRCA1/2 mutations, although some researchers believe it is necessary to test the validity
of assumptions underlying the general prohibition of testing children for
genetic mutations associated with breast and ovarian cancers and other adult-onset diseases.[56-58] In one study, 20 children (aged 11–17 years) of a selected group of mothers undergoing genetic testing (80% of whom previously had breast cancer and all of whom had discussed BRCA1/2 testing with their children) completed self-report questionnaires on their health beliefs and attitudes toward cancer, feelings related to cancer, and behavioral problems.[59] Ninety percent of children thought they would want cancer risk information as adults; half worried about themselves or a family member developing cancer. There was no evidence of emotional distress or behavioral problems.

What People Bring to Genetic Testing: Impact of Risk Perception, Health Beliefs, and Personality Characteristics

The emerging literature in this area suggests that risk perceptions,
health beliefs, psychological status, and personality characteristics are important factors in
decision-making about breast/ovarian cancer genetic testing. Many women
presenting at academic centers for BRCA1/BRCA2 testing arrive with a strong belief
that they have a mutation, having decided they want genetic testing, but
possessing little information about the risks or limitations of testing.[60] Most mean scores of psychological functioning at baseline for subjects in genetic counseling studies were within normal limits.[61] Nonetheless, a subset of subjects in many genetic counseling studies present with elevated anxiety, depression, or cancer worry.[62,63] Identification of these individuals is essential to prevent adverse outcomes. In a study of 205 women pursuing genetic counseling, interactions among cancer worry, breast cancer risk perception, and perceived severity of having a breast cancer gene mutation were found such that those with high worry, high breast cancer risk perception, and low perceived severity were twice as likely to follow through with BRCA1/BRCA2 testing than others.[64]

A general tendency to overestimate inherited risk of breast and ovarian cancer
has been noted in at-risk populations,[65-67] in cancer patients,[66,68,69] in spouses of breast and ovarian cancer patients,[70] and among
women in the general population.[71-73] but underestimation of breast cancer risk in higher-risk and average-risk women also has been reported.[74] This overestimation may encourage a belief that
BRCA1/BRCA2 genetic testing will be more informative than it is currently thought
to be. Some evidence exists that even counseling does not dissuade women at
low to moderate risk from the belief that BRCA1 testing could be valuable.[36]
Overestimation of both breast and ovarian cancer risk has been associated with nonadherence to physician-recommended screening practices.[75,76] A meta-analysis of 12 studies of outcomes of genetic counseling for breast/ovarian cancer showed that counseling improved the accuracy of risk perception.[77]

Women appear to be the prime communicators within families about the family
history of breast cancer.[78] Higher numbers of maternal versus paternal
transmission cases are reported,[79] likely due to family communication
patterns, to the misconception that breast cancer risk can only be transmitted
through the mother, and to the greater difficulty in recognizing paternal
family histories because of the need to identify more distant relatives with
cancer. In an analysis of 2,505 women participating in the Family Healthware Impact Trial,[80] not only was evidence of underreporting of paternal family history identified, but also women reported a lower level of perceived breast cancer risk with a paternal versus maternal breast cancer family history.[81] Physicians and counselors taking a family history are encouraged to
elicit paternal and maternal family histories of breast, ovarian, or
other associated cancers.[78]

The accuracy of reported family history of breast or ovarian cancer varies;
some studies found levels of accuracy above 90%,[82,83] with others finding
more errors in the reporting of cancer in second-degree or more distant
relatives [84] or in age of onset of cancer.[85] Less accuracy has been found in the reporting of cancers other
than breast cancer. Ovarian cancer history was reported with 60% accuracy in
one study compared with 83% accuracy in breast cancer history.[86] Providers
should be aware that there are a few published cases of Munchausen syndrome in
reporting of false family breast cancer history.[87] Much more common is
erroneous reporting of family cancer history due to unintentional errors or
gaps in knowledge, related in some cases to the early death of potential
maternal informants about cancer family history.[78]
(Refer to the Taking a Family History section of the Cancer Genetics Risk Assessment and Counseling summary for more information.)

Targeted written,[88,89] video, CD-ROM, interactive computer program,[90-94] and culturally targeted educational materials [95-97] may be effective and efficient methods of increasing knowledge about the pros and cons of genetic testing. Such supplemental materials may allow more efficient use of the time allotted for pretest education and counseling by genetics and primary care providers and may discourage individuals without appropriate indication of risk from seeking genetic testing.[88]

Genetic Counseling for Hereditary Predisposition to Breast Cancer

Counseling for breast cancer risk typically involves individuals with family
histories that are potentially attributable to BRCA1 or BRCA2. It also, however,
may include individuals with family histories of Li-Fraumeni syndrome, ataxia-telangiectasia, Cowden syndrome, or Peutz-Jeghers syndrome.[98] (Refer to the High-Penetrance Breast and/or Gynecologic Cancer Susceptibility Genes section of this summary for more information.)

Management strategies for carriers may involve decisions about the nature, frequency, and
timing of screening and surveillance procedures, chemoprevention, risk-reducing surgery, and use of
hormone replacement therapy (HRT). The utilization of breast conservation and
radiation as cancer therapy for women who are carriers may be influenced by knowledge of mutation status. (Refer to the Clinical Management of BRCA Mutation Carriers section of this summary for more information.)

Counseling also includes consideration of related psychosocial concerns and
discussion of planned family communication and the responsibility to warn other
family members about the possibility of having an increased risk of breast,
ovarian, and other cancers. Data are emerging that individual responses to being tested as adults are influenced by the results status of other family members.[99,100] Management of anxiety and distress are important
not only as quality-of-life factors, but also because high anxiety may
interfere with the understanding and integration of complex genetic and medical
information and adherence to screening.[101-103] The limited number of
medical interventions with proven benefit to mutation carriers provides further
basis for the expectation that mutation carriers may experience increased
anxiety, depression, and continuing uncertainty after disclosure of genetic
test results.[104] Formal, objective evaluation of these outcomes are now
emerging. (Refer to the Emotional Outcomes and Behavioral Outcomes sections of this summary for more information.)

Published descriptions of counseling programs for BRCA1 (and subsequently for
BRCA2) testing include strategies for gathering a family history, assessing
eligibility for testing, communicating the considerable volume of relevant
information about breast/ovarian cancer genetics and associated medical and
psychosocial risks and benefits, and discussion of specialized ethical
considerations about confidentiality and family communication.[3,105-111]
Participant distress, intrusive thoughts about cancer, coping style, and social
support were assessed in many prospective testing candidates. The psychosocial
outcomes evaluated in these programs have included changes in knowledge about
the genetics of breast/ovarian cancer after counseling, risk comprehension,
psychological adjustment, family and social functioning, and reproductive and
health behaviors.[112] A Dutch study of communication processes and satisfaction levels of counselees going through cancer genetic counseling for inherited cancer syndromes indicated that asking more medical questions (by the counselor), providing more psychosocial information, and longer eye contact by the counselor were associated with lower satisfaction levels. The provision of medical information by the counselor was most highly related to satisfaction and perception that needs have been fulfilled.[113] Additional research is needed on how to adequately address the emotional needs and feelings of control of counselees.

Many of the psychosocial outcome studies involve specialized, highly selected
research populations, some of which were utilized to map and clone BRCA1 and
BRCA2. One such example is K2082, an extensively studied kindred of more than 800
members of a Utah Mormon family in which a BRCA1 mutation accounts for the
observed increased rates of breast and ovarian cancer. A study of the
understanding that members of this kindred have about breast/ovarian cancer
genetics found that, even in breast cancer research populations, there was
incomplete knowledge about associated risks of colon and prostate cancer, the
existence of options for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO),
and the complexity of existing psychosocial risks.[3]
A meta-analysis of 21 studies found that genetic counseling was effective in increasing knowledge and improved the accuracy of perceived risk. Genetic counseling did not have a statistically significant long-term impact on affective outcomes including anxiety, distress, or cancer-specific worry and the behavioral outcome of cancer surveillance activities.[61] These prospective studies, however, were characterized by a heterogeneity of measures of cancer-specific worry and inconsistent findings in effects of change from baseline.[61]

It is not yet clearly established to what extent findings derived from special
research populations, at least some of which have long awaited genetic testing
for breast/ovarian cancer risk, are generalizable to other populations. For
example, there are data to suggest that the BRCA1/BRCA2penetrance estimates
derived from these dramatically affected families are substantial overestimates
and do not apply to most families presenting for counseling and
possible testing.[114]

Emotional Outcomes

Studies conducted to date of psychological outcomes associated with
genetic testing for mutations in breast/ovarian cancer predisposition genes have shown
low levels of distress among those found to be carriers and even lower levels
among noncarriers.[88,115-118] A systematic review found that the studies assessing
measures of distress (9 of 11 studies) found no change, or a decrease, in those
parameters (including anxiety, depression, general distress, and situation
distress) in people who had undergone testing at assessments done at 1 month or
less, and 3 to 6 months later.[119] One follow-up study from the United Kingdom measured levels of cancer-related worry, general mental health, risk perception, intrusive or avoidant thoughts, and risk-management behaviors at baseline and 1, 4, and 12 months after results were provided. This study included 202 unaffected women and 59 unaffected men, of whom 91 tested positive and 170 tested negative. Results showed that while female noncarriers had significant (P < .001) reductions in cancer-related worry, female carriers younger than 50 years had an increase in cancer-related worry 1 month posttesting. These levels returned to baseline by 12 months but remained higher than noncarrier levels throughout the 12-month period. Female carriers engaged in more posttest screening than noncarriers (92% vs. 30%) within 12 months of test results disclosure. Thirty carriers had RRM and/or RRSO within the same time period.[120] A slightly smaller subset of this cohort was assessed again for cancer-related worry, general mental health, and risk-management behaviors 3 years after genetic test result disclosure. Among those who returned the questionnaire were 154 women and 39 males, including 71 carriers and 122 noncarriers. The level of distress and cancer worry was similar between carriers and noncarriers. Female carriers had higher distress levels at 3 years versus 1 year postdisclosure, but their level of cancer worry decreased significantly over the same time period. In female noncarriers, although the level of cancer worry had decreased from baseline to 1 year postdisclosure, these levels returned to baseline by 3 years.[121] The authors did not comment on contextual factors that might influence distress and cancer worry levels. Another study reported that, compared with pretest levels, mean scores on 1-year posttest measures of cancer-specific distress and state-anxiety decreased significantly among noncarriers, while scores on these measures and on a measure of general distress did not change among BRCA1/BRCA2 carriers.[122] One long-term study of 65 female participants explored the psychosocial consequences of carrying a BRCA1/BRCA2 mutation 5 years after genetic testing. Carriers did not differ from noncarriers on several distress measures. Although both groups showed significant increases in depression and anxiety compared with 1 year postdisclosure, these scores remained within normal limits for the general population.[123] Caution is advised by authors of these studies in interpretation of
the results as they are all from programs in which results disclosure was
preceded by extensive genetic counseling about risks and benefits of BRCA1/BRCA2
testing, psychological assessment, and in some cases exclusion of a few
individuals who appeared highly distressed.[3] Intrusive thoughts (measured
by the Impact of Event Scale [IES]) [124] about cancer diminished after results
disclosure for both mutation-positive and mutation-negative individuals in one
Dutch study.[125]

Some studies have examined reactions to BRCA testing several years after the receipt of results. Two U.S.-based studies have reported similar findings among women who were surveyed more than 3 years after receipt of BRCA test results.[126,127] In a cross-sectional study,[126] 167 women who were surveyed more than 4 years after receiving BRCA test results reported low levels of genetic testing–specific concerns, as measured using the Multidimensional Impact of Cancer Risk Assessment Scale.[128] Approximately 74% of women reported no distress; 41% reported no uncertainty about their cancer risk, screening decisions, and options for risk management and prevention; and 51% reported positive experiences suggestive of low adverse reactions pertaining to family support and communication.[126] In multivariate regression models, mutation carriers were significantly more likely to experience distress than were noncarriers. Time since disclosure of test result significantly predicted uncertainty but not distress, such that more time since disclosure corresponded to less uncertainty. In a second study, 464 women were followed prospectively for a median of 5 years (range: 3.4–9.1 years) after testing. Among both affected and unaffected participants, BRCA carriers reported significantly higher levels of distress, uncertainty (affected only), perceived stress (affected only), and lower positive testing experiences (unaffected only) than women who received negative results.[127] Although both studies reported greater distress among BRCA carriers than among noncarriers, the level of distress was not reflective of clinically significant dysfunction.

A prospective Australian study evaluated the psychological impact of genetic testing at baseline, 7 to 10 days, 4 months, and 12 months in 60 women of AJ heritage (10 with breast cancer, 50 unaffected). Of the 43 women who opted to learn their test results, 97% felt pleased to have had the test and, at 12 months of follow-up, none regretted having been tested. Seventeen women opted not to receive their results and had significantly lower levels of breast cancer anxiety than did those who opted to receive their results. Women with no history of cancer who opted to learn their results showed a progressive decrease in breast cancer anxiety over the 12-month study period compared with baseline measures. There was also no statistically significant difference in measures of depression and generalized anxiety from baseline to the follow-up assessments.[129] However, only 7 of 43 women had deleterious mutations, which may influence interpretation of test results.

Despite generally positive findings regarding diminished distress in tested individuals, most studies also report increased distress among small subsets of tested individuals. Most, but not all, of these increases are within the normal range of distress. Increased distress has been noted by individuals receiving both positive and negative test results. Studies suggest that the psychological impact of an individual test result is highly influenced by the test result status of other family members. A 1999 study found that an individual’s response to learning his or her own BRCA1/BRCA2 test result was significantly influenced by his or her gender and by the genetic test result status of other family members. Adverse, immediate outcomes were experienced by male carriers who were the first tested in their family or by noncarrier men whose siblings were all positive.
In addition, female carriers who were the first in their families to be tested or whose siblings were all negative had significantly higher distress than other female carriers.[99] Another study found that spousal anxiety about genetic testing and supportiveness differentiated the impact of BRCA1/BRCA2 test results. When the spouse was highly anxious and unsupportive in style, the mutation carrier had significantly higher levels of distress. These studies illustrate that genetic test results are not received in a vacuum, and that researchers need to consider the context of the tested individual in determining which individuals applying for genetic testing may require additional emotional support.[100]

In another study, depression rates postdisclosure were unchanged for mutation
carriers and markedly decreased for noncarriers.[46] An analysis of the
distress of individuals receiving BRCA1 results in the context of their siblings'
results, however, revealed patterns of response suggesting that certain
subgroups of tested individuals have markedly increased levels of distress
after disclosure that were not apparent when the analysis focused only on
comparing the mean scores for carriers versus noncarriers.[99] Early
optimistic findings may not sufficiently reflect the true complexity of
response to disclosure of BRCA1/BRCA2 test results. Female carriers who had no
carrier siblings had distress scores (IES) similar to those found in cancer
patients 10 weeks after their diagnosis. The distress of male subjects was
highly correlated with the status of their siblings’ test results or lack
thereof.[99] One pilot study suggested that women diagnosed more recently were
more distressed after counseling.[130] A survey of women enrolled in a high-risk clinic found that heightened levels of distress may be more related to living with the awareness of a familial risk of cancer than with the genetic testing process itself. Obtaining genetic testing may be less stressful than living with the awareness of familial risk of cancer.[131] (Refer to the PDQ Supportive Care summaries on Depression and Adjustment to Cancer: Anxiety and Distress for more detailed information about depression and anxiety associated with a cancer diagnosis.) Case descriptions have supported the
importance of family relationships and test outcomes in shaping the distress of
tested individuals.[132,133]

Although there are not yet reports of large-scale studies of the reactions of affected individuals to genetic testing, there are indications from several smaller studies that affected individuals who undergo genetic counseling and testing experience more distress than had been expected by professionals [134,135] and are less able themselves to anticipate the intensity of their reactions after result disclosure.[136] Female mutation carriers who have had breast cancer are often surprised by their high risk of ovarian cancer. Women mutation carriers who have had breast cancer worried more than unaffected women about developing ovarian cancer, though, in general, worry about ovarian cancer risk was found to be unrealistically low.[135] In addition, some distress related to the burden of conveying genetic information to relatives has been noted among those who are the first in their families to be tested.[134,137]

The long-term effect of uninformative BRCA1/BRCA2 test results (BRCA1/BRCA2 negative, negative on a panel of three Ashkenazi founder mutations, or detecting a variant of uncertain significance) was examined in 209 women recruited from one of two comprehensive cancer centers or a community hospital.[138] These women had a personal history of breast or ovarian cancer and were assessed at pretesting, 1-, 6-, and 12-months postdisclosure. Distress was low at each time point, and declined from pretest to post-disclosure, remaining stable and low thereafter. No clinical cut-offs were reported. Those who reported higher general distress associated with cancer risk, risk-reduction efforts, and family communication and lower confidence in dealing with these issues, and those who expected to carry a deleterious mutation, had greater decisional conflict related to managing their cancer risk through 1-year posttest. In another study of 182 women drawn from this sample, most (84%) had made a risk management decision within 6 months of test result disclosure. Those who were delayed in making a risk management decision reported greater feelings of decisional uncertainty, dissatisfaction, and lack of confidence, yet there was also a high level of reported decisional conflict even among those who were early or intermediate decision-makers. Increased depression levels postdisclosure predicted increased risk of delay in risk management decision-making.[139]

Several studies have compared the provision of breast cancer genetics services by different providers and the psychological impact on women at high and low risk of cancer. In a study of 735 women at all hereditary breast/ovarian cancer risk levels, the services of a multidisciplinary team of genetics specialists was compared with services provided by surgeons. There were no significant differences between groups in anxiety, cancer worry, or perceived risk.[140] In a Scottish study of 373 participants, an alternative model of cancer genetics services using genetics nurse specialists in community-based services was compared with standard genetics regional services. There was no difference in cancer worry or change in health behaviors between the two groups. Cancer worry decreased for both groups over a 6-month period. Women who dropped out of the study tended to be in the nurse provider arm or were at low risk of breast cancer.[141] In a small U.S. study, an evaluation of nurses and genetic counselors as providers of education about breast cancer susceptibility testing was conducted to compare outcomes of pretest education about breast cancer susceptibility. Four genetic counselors and two nurses completed specialized training in cancer genetics. Women receiving pretest education from nurses were as satisfied with information received and had equal degrees of perceived autonomy and partnership. The study findings suggest that with proper training and supervision, both genetic counselors and nurses can be effective in providing pretest education to women considering genetic susceptibility testing for breast cancer risk.[142]

There has been little empirical research in the communication of risk
assessments to individuals at risk of breast/ovarian cancer syndromes. When
asked to choose a preferred method, individuals undergoing genetic counseling
for breast and ovarian cancer appear to prefer quantitative to qualitative
presentation of risk information.[143,144] One study indicated that most women wanted information given both ways.[68] Information about the risk of
developing breast cancer among women with a family history of breast cancer may
be more accurately recalled when presented as odds ratios (ORs), rather than in other
forms.[145]

There is a small but growing body of literature on the use of decision aids as an adjunct to standard genetic counseling to assist patients in making informed decisions about genetic testing. One study measured the effectiveness of a decision aid for BRCA1/BRCA2 genetic testing given to women at the end of their first genetic counseling consultation. At 1 week and 6 months follow-up, the decision aid had no effect on informed choice, decisional regret, or actual genetic testing decision. However, women who received the decision aid had significantly higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet. The decision aid also helped those women who did not have their blood drawn for genetic testing at the first visit to clarify their values about their testing decision.[146]

Preferences for delivery of breast cancer genetic testing are reported in one
study [144] to include pretest counseling conducted by a genetic counselor (42%) or
oncologist (22%) rather than by a primary care physician (6%), nurse (12%), or
gynecologist (5%). Patients in that study preferred results disclosure by an
oncologist. Younger women especially expressed a need for individual
consideration of their personal values and goals or potential emotional
reactions to testing; 67% believed emotional support and counseling were a
necessary part of posttest counseling. Most women (82%) wanted to
be able to self-refer for genetic testing, without a physician referral.

Family Effects

Family communication about genetic testing and hereditary risk

Family communication about genetic testing for cancer susceptibility, and
specifically about the results of BRCA1/BRCA2 genetic testing, is complex; there are
few systematic data available on this topic. Gender appears to be an important variable in family communication and psychological outcomes. One
study documented that female carriers are more likely to disclose their status
to other family members (especially sisters and children aged 14–18 years) than
are male carriers.[147] Among males, noncarriers were more likely than carriers
to tell their sisters and children the results of their tests. BRCA1/BRCA2
carriers who disclosed their results to sisters had a slight decrease in
psychological distress, compared with a slight increase in distress for carriers
who chose not to tell their sisters. One study found that men reported greater difficulty disclosing mutation-positive results to family members than women (90% vs. 70%).[148]

Family communication of BRCA1/BRCA2 test results to relatives is another factor affecting participation in testing. There have been more studies of communication with first-degree relatives and second-degree relatives than with more distant family members. One study investigated the process and content of communication among sisters about BRCA1/BRCA2 test results.[149] Study results suggest that both mutation carriers and women with uninformative results communicate with sisters to provide them with genetic risk information. Among relatives with whom genetic test results were not discussed, the most important reason given was that the affected women were not close to their relatives. Studies found that women with a BRCA mutation more often shared their results with their mother and adult sisters and daughters than with their father and adult brothers and sons.[78,150-153] A study that evaluated communication of test results to first-degree relatives at 4 months postdisclosure found that women aged 40 years or older were more likely to inform their parents of test results compared with younger women. Participants also were more likely to inform brothers of their results if the BRCA mutation was inherited through the paternal line.[151] Another study found that disclosure was limited mainly to first-degree relatives, and dissemination of information to distant relatives was problematic.[154] Age was a significant factor in informing distant relatives with younger patients being more willing to communicate their genetic test result.[149,150,154]

A few in-depth qualitative studies have looked at issues associated with family communication about genetic testing. Although the findings from these studies may not be generalizable to the larger population of at-risk persons, they illustrate the complexity of issues involved in conveying hereditary cancer risk information in families.[155] On the basis of 15 interviews conducted with women attending a familial cancer genetics clinic, the authors concluded that while women felt a sense of duty to discuss genetic testing with their relatives, they also experienced conflicting feelings of uncertainty, respect, and isolation. Decisions about whom in the family to inform and how to inform them about hereditary cancer and genetic testing may be influenced by tensions between women's need to fulfill social roles and their responsibilities toward themselves and others.[155] Another qualitative study of 21 women who attended a familial breast and ovarian cancer genetics clinic suggested that some women may find it difficult to communicate about inherited cancer risk with their partners and with certain relatives, especially brothers, because of those persons’ own fears and worries about cancer.[153] This study also suggested that how genetic risk information is shared within families may depend on the existing norms for communicating about cancer in general. For example, family members may be generally open to sharing information about cancer with each other, may selectively avoid discussing cancer information with certain family members to protect themselves or other relatives from negative emotional reactions, or may ask a specific relative to act as an intermediary to disclosure of information to other family members.[156] The potential importance of persons outside the family, such as friends, as both confidantes about inherited cancer risk information and as sources of support for coping with this information was also noted in the study.[153]

A study of 31 mothers with a documented BRCA mutation explored patterns of dissemination to children.[157] Of those who chose to disclose test results to their children, age of offspring was the most important factor. Fifty percent of the children who were told were aged 20 to 29 years and slightly more than 25% of the children were aged 19 years or younger. Sons and daughters were notified in equal numbers. More than 70% of mothers informed their children within a week of learning their test result. Ninety-three percent of mothers who chose not to share their results with their children indicated that it was because their children were too young. These findings were consistent with three other studies showing that children younger than 13 years were less likely to be informed about test
results compared with older children.[151,158,159] Another study of 187 mothers undergoing BRCA1/BRCA2 testing evaluated their need for resources to prepare for a facilitated conversation about sharing their BRCA1/BRCA2 testing results with their children. Seventy-eight percent of mothers were interested in three or more resources, including literature (93%), family counseling (86%), talk to prior participants (79%), and support groups (54%).[158]

A longitudinal study of 153 women self-referred for genetic testing for BRCA1 and BRCA2 mutations and 118 of their partners evaluated communication about genetic testing and distress before testing and at 6 months
posttesting.[160] The study found that most couples discussed the decision to undergo testing (98%), most test participants felt their partners were supportive, and most women disclosed test results to their partners (97%, n = 148). Test participants who felt their partners were supportive during pretest discussions experienced less distress after disclosure, and
partners who felt more comfortable sharing concerns with test participants pretest experienced less distress after disclosure. Six-month follow-up revealed that 22% of participants felt the need to talk about the testing experience with their partners in the week before the interview. Most participants (72%, n = 107) reported comfort in sharing concerns with their partners, and 5% (n = 7) reported relationship strain as a result of genetic testing. In couples in which the woman had a positive genetic test result, more relationship strain, more protective buffering of their partners, and more discussion of related concerns were reported than in couples in which the woman had a true-negative or uninformative result.[160]

There is a small but growing body of literature regarding psychological effects in men who have a family history of breast cancer and who are considering or have had BRCA testing. A qualitative study of 22 men from 16 high-risk families in Ireland revealed that more men in the study with daughters were tested than men without daughters. These men reported little communication with relatives about the illness, with some men reporting being excluded from discussion about cancer
among female family members. Some men in the study also reported actively avoiding open discussion with daughters and other relatives.[161] In contrast, a study of 59 men testing positive for a BRCA1/BRCA2 mutation found that most men participated in family discussions about breast and/or ovarian cancer. However, fewer than half of the men participated in family discussions about risk-reducing surgery. The main reason given for having BRCA testing was concern for their children and a need for certainty about whether they could have transmitted the mutation to their children. In this study, 79% of participating men had at least one daughter. Most of these men described how their relationships had been strengthened after receipt of BRCA results, helping communication in the family and greater understanding.[162] Men in both studies expressed fears of developing cancer themselves. Irish men especially reported
fear of cancer in sexual organs.

Family functioning

One study assessed 212 individuals from 13 hereditary breast and ovarian cancer families who received genetic counseling and were offered BRCA1/BRCA2 testing for documented mutation in the family. Individuals who were not tested were found 6 to 9 months later to have significantly greater increases in family expressiveness and cohesiveness compared with those who were tested. Persons who were randomly assigned to a client-centered versus problem-solving genetic counseling intervention had a significantly greater reduction in conflict, regardless of the test decision.[49]

Partners of high-risk women

Many studies have looked at the psychological effects in women of having a high risk of developing cancer, either on the basis of carrying a BRCA1/BRCA2 mutation or having a strong family history of cancer. Some studies have also examined the effects on the partners of such women.

A Canadian study assessed 59 spouses of women found to have a BRCA1/BRCA2 mutation. All were supportive of their spouses’ decision to undergo genetic testing and 17% wished they had been more involved in the genetic testing process. Spouses who reported that genetic testing had no impact on their relationship had long-term relationships (mean duration 27 years). Forty-six percent of spouses reported that their major concern was of their partner dying of cancer. Nineteen percent were concerned their spouse would develop cancer and 14% were concerned their children would also be BRCA1/BRCA2 mutation carriers.[163]

In a U.S. study, 118 partners of women who underwent genetic testing for mutations in BRCA1 and BRCA2 completed a survey before testing and then again 6 months after result disclosure. At 6 months, only 10 partners reported that they had not been told of the test result. Ninety-one percent reported that the testing had not caused strain on their relationship. Partners who were comfortable sharing concerns before testing experienced less distress after testing. Protective buffering was not found to impact distress levels of partners.[160]

An Australian study of 95 unaffected women at high risk of developing breast and/or ovarian cancer (13 mutation carriers and 82 with unknown mutation status) and their partners showed that although the majority of male partners had distress levels comparable to a normative population sample, 10% had significant levels of distress that indicated the need for further clinical intervention. Men with a high monitoring coping style and greater perceived breast cancer risk for their wives reported higher levels of distress. Open communication between the men and their partners and the occurrence of a cancer-related event in the wife’s family in the last year were associated with lower distress levels. When men were asked what kind of information and support they would like for themselves and their partners, 57.9% reported that they would like more information about breast and ovarian cancer, and 32.6% said they would like more support in dealing with their partner's risk. Twenty-five percent of men had suggestions on how to improve services for partners of high-risk women, including strategies on how to best support their partner, greater encouragement from health care professionals to attend appointments, and meeting with other partners.[164]

A review of this literature reported that the BRCA testing process may be distressing for male partners, particularly for those with spouses identified as carriers. Male partner distress appears to be associated with their beliefs about the woman’s breast cancer risk, lack of couple communication, and feelings of alienation from the testing process.[165]

At-risk males

A review of the literature on the experiences of males in BRCA1 and BRCA2 mutation–positive families reported that while the data are limited, men from mutation-positive families are less likely than females to participate in communication regarding genetics at every level, including the counseling and testing process. Men are less likely to be informed of genetic test results received by female relatives, and most men from these families do not pursue their own genetic testing.[166]

A study of Dutch men at increased risk of having inherited a BRCA1 mutation reported a tendency for the men to deny or minimize the emotional effects of their risk status, and to focus on medical implications for their female relatives. Men in these families, however, also reported considerable distress in relation to their female relatives.[167] In another study of male psychological functioning during breast cancer testing, 28 men belonging to 18 different high-risk families (with a 25% or 50% risk of having inherited a BRCA1/BRCA2 mutation) participated. The study purpose was to analyze distress in males at risk of carrying a BRCA1/BRCA2 mutation who
applied for genetic testing. Of the men studied, most had low
pretest distress; scores were lowest for men who were optimistic or who did not have daughters. Most mutation carriers had normal levels of anxiety and depression and reported no guilt, though some anticipated increased distress and feelings of responsibility if their daughters developed breast or ovarian cancer. None of the noncarriers reported feeling guilty.[168] In one study,[162] adherence to recommended screening guidelines after testing was analyzed. In this study, more than half of male carriers of mutations did not adhere to the screening guidelines recommended after disclosure of genetic test results. These findings are consistent with those for female carriers of BRCA1/BRCA2 mutations.[162,169]

A multicenter U.K. cohort study examined prospective outcomes of BRCA1/BRCA2 testing in 193 individuals, of which 20% were men aged 28 to 86 years. Men’s distress levels were low, did not differ among carriers and noncarriers, and did not change from baseline (before genetic testing) to the 3-year follow-up. Twenty-two percent of male mutation carriers received colorectal cancer screening and 44% received prostate cancer screening;[121] however, it is unclear whether men in this study were following age-appropriate screening guidelines.

Children

Several studies have explored communication of BRCA test results to at-risk children. Across all studies, the rate of disclosure to children ranging in age from 4 to 25 years is approximately 50%.[150,151,154,158,170-173] In general, age of offspring was the most important factor in deciding whether to disclose test results. In one study of 31 mothers disclosing their BRCA test results, 50% of the children who were informed of the results were aged 20 to 29 years and slightly more than 25% of the children were aged 19 years or younger. Sons and daughters were notified in equal numbers.[157] Similarly, in another study of 42 female BRCA mutation carriers, 83% of offspring older than age 18 years were told of the results, while only 21% of offspring aged 13 years or younger were told.[158]

Several studies have also looked at the timing of disclosure to children after parents receive their test results. Although the majority of children were told within a week to several months after results disclosure,[151,157,158] some parents chose to delay disclosure.[158] Reasons for delaying disclosure included waiting for the child to get older, allowing time for the parent to adjust to the information, and waiting until results could be shared in person (in the case of adult children living away from home).[158]

One study looked at the reaction of children to results disclosure or the effect on the parent-child relationship of communicating the results.[158] With regard to offspring’s understanding of the information, almost half of parents from one study reported that their child did not appear to understand the significance of a positive test result, although older children were reported to have a better understanding. This same study also showed that 48% of parents reported at least one negative reaction in their child, ranging from anxiety or concern (22%) to crying and fear (26%). It should be noted, however, that in this study children's level of understanding and reactions to the test result were measured qualitatively and based only on the parents' perception. Also, given the retrospective design of the study, there was a potential for recall bias. There were no significant differences in emotional reaction depending on age or gender of the child. Lastly, 65% of parents reported no change in their relationship with their child, while 5 parents (22%) reported a strengthening of their relationship.

Another study of 187 mothers undergoing BRCA1/BRCA2 testing evaluated their need for resources to prepare for a facilitated conversation about sharing their BRCA1/BRCA2 testing results with their children. Seventy-eight percent of mothers were interested in three or more resources, including literature (93%), family counseling (86%), talking to prior participants (79%), and support groups (54%).[174]

Testing for BRCA1/BRCA2 has been almost universally limited to adults older than 18
years. The risks of testing children for adult-onset disorders (such as breast
and ovarian cancer), as inferred from developmental data on children’s medical
understanding and ability to provide informed consent, have been outlined in
several reports.[50-53] Surveys of parental interest in testing children
for adult-onset hereditary cancers suggest that parents are more eager to
test their children than to be tested themselves for a breast cancer gene,
suggesting potential conflicts for providers.[175,176] In a general population
survey in the United States, 71% of parents said that it was moderately, very,
or extremely likely that if they carried a breast-cancer predisposing mutation,
they would test a 13-year-old daughter now to determine her breast cancer
gene status.[175] To date, no data exist on the testing of children for
BRCA1/BRCA2, though some researchers believe it is necessary to test the validity
of assumptions underlying the general prohibition of testing of children for
breast/ovarian cancer and other adult-onset disease genes.[56-58] In one study, 20 children (aged 11–17 years) of a selected group of mothers undergoing genetic testing (80% of whom previously had breast cancer and all of whom had discussed BRCA1/BRCA2 testing with their children) completed self-report questionnaires on their health beliefs and attitudes toward cancer, feelings related to cancer, and behavioral problems.[59] Ninety percent of children thought they would want cancer risk information as adults; half worried about themselves or a family member developing cancer. There was no evidence of emotional distress or behavioral problems. Another study by this group [172] found that 1 month after disclosure of BRCA1/BRCA2 genetic test results, 53% of 42 enrolled mothers of children aged 8 to 17 years had discussed their result with one or more of their children. Age of the child rather than mutation status of the mother influenced whether they were told, as did family health communication style.

In one study, participants
who told children younger than 13 years about their carrier status had
increased distress, and those who did not tell their young children experienced
a slight decrease in distress. Communication with young children was found to be influenced by developmental variables such as age and style of parent/child communication.[172]

Prenatal diagnosis and preimplantation genetic diagnosis

The possibility of transmitting a mutation to a child may pose a concern to families affected by history of breast/ovarian cancer (HBOC),[177] perhaps to the extent that some carriers may avoid childbearing.[178,179] These concerns also may prompt women to consider using prenatal diagnosis methods to help reduce the risk of transmission.[177,180] Prenatal diagnosis is an encompassing term used to refer to any medical procedure conducted to assess the presence of a genetic disorder in a fetus. Methods include amniocentesis and chorionic villous sampling (CVS).[181,182] Both procedures carry some risk of miscarriage and some evidence suggests fetal defects may result from using these tests.[181,182] Moreover, discovering the fetus is a carrier for a genetic defect may impose a difficult decision for couples regarding pregnancy continuation or termination. An alternative to these tests is preimplantation genetic diagnosis (PGD), a procedure used to test fertilized embryos for genetic disorders before uterine implantation,[177,183,184] thereby avoiding the potential dangers associated with amniocentesis and CVS and the decision to terminate a pregnancy. Using the information obtained from the genetic testing, potential parents can decide whether or not to implant. PGD can be used to detect mutations in hereditary cancer predisposing genes, including BRCA.[177,180]

In the United States, a series of studies have evaluated awareness, interest (e.g., would consider using PGD), and attitudes related to PGD among members of Facing Our Risk of Cancer Empowered (FORCE), an advocacy organization focused on persons at increased risk of HBOC.[177,180,185] The first study was a Web-based survey of 283 members,[177] the second included 205 attendees of the 2007 annual FORCE conference,[180] and the third was a Web-based survey of 962 members.[185,186] These studies have documented low levels of awareness, with 20% to 32% of study respondents reporting having heard of PGD before study participation.[180,185] With respect to interest in PGD, the first study [177] found only 13% of women would be likely to use PGD, whereas, 33% of respondents in the subsequent FORCE studies reported that they would consider using PGD.[180,185] In the third FORCE-based study (n = 962),[185] multivariable analysis revealed PGD interest was associated with the desire to have more children, having previously had any prenatal genetic test, and previous awareness of PGD. Attitudinal predictors of interest in PGD included agreement that others at risk of HBOC should be offered PGD; the belief that PGD is acceptable for persons at risk of HBOC; the belief that PGD information should be given to individuals at risk of HBOC; and endorsement of PGD benefits of having children without genetic mutations and eliminating genetic diseases.

Conversely, those who indicated that PGD was “too much like playing God” and reported that they considered PGD in the context of religion, had less interest in PGD.

The U.K. Human Fertilization and Embryology authority has approved the use of PGD for hereditary breast and ovarian cancer. In a sample of 102 women with a BRCA mutation, most were supportive of PGD but only 38% of the women who had completed their families would consider it for themselves had PGD been available, and only 14% of women who were contemplating a future pregnancy would consider PGD.[187] In a study of 77 individuals undergoing BRCA testing as part of a multicenter cohort study in Spain, 61% of respondents reported they would consider PGD. Factors associated with PGD interest were age 40 years and older and had a prior cancer diagnosis.[188]

In France, couples who obtain authorization from a multidisciplinary prenatal diagnosis team may access PGD free of charge as a benefit of their national health care system. However, no BRCA carriers have been authorized to use PGD. In a national study of 490 unaffected BRCA mutation carriers of childbearing age (women aged 18–49 years; men aged 18–69 years), 16% stated that BRCA test results had altered their ongoing plans for childbearing.[189] Upon qualitative analysis of written comments provided by some respondents,
the primary impact was related to accelerating the timing of pregnancy, feelings of guilt about possibly passing on the mutation to offspring, and having future children. In response to a
hypothetical scenario in which PGD was readily available, 33% of participants reported that they would undergo PGD. Factors associated with this intention were having no future reproductive plans at the time of the survey, feeling pregnancy termination was an acceptable option in the context of identifying a BRCA mutation, and having fewer cases of breast and/or ovarian cancer in the family. When presented with questions about expectations about delivery of PGD or prenatal diagnosis (PND) information, 85% of respondents felt it should be provided along with BRCA test results; 45% felt that it should be provided when carriers decide to have children. Respondents stated
that they would expect this information to be delivered by cancer geneticists (92%), obstetrician/gynecologists (76%), and general practitioners (48%).

A small (N = 25) qualitative study of BRCA mutation–positive women of reproductive age who underwent genetic testing before having children evaluated how their BRCA status influenced their attitudes about reproductive genetic testing (both PGD and PND) and decisions about having children.[190] In this study, the decision to undergo BRCA testing was primarily motivated by the desire to manage one’s personal cancer risk, rather than a desire to inform future reproductive decisions. The perceived severity of HBOC influenced concerns about passing on a BRCA mutation to children and also influenced willingness to consider PGD or PND and varied based on personal experience. Most did not believe that BRCA mutation–positive status was a reason to terminate a pregnancy. As observed in prior studies, knowledge of reproductive options varied; however, there was a tendency among participants to view PGD as more acceptable than PND with regard to termination of
pregnancy. Decisions regarding the pros and cons of PGD versus PND with termination of pregnancy were driven primarily by personal preferences and experiences, rather than by morality judgments. For example, women were deterred from PGD based on the need to undergo in vitro fertilization and to take hormones that might increase cancer risk and based on the observed
experiences of others who underwent this procedure.

One study has examined these issues among high-risk men recruited from FORCE and Craigslist (a bulletin board Web site) (N = 228).[191] Similar to the previous studies of women, only 20% of men were aware of PGD before survey participation. In a multivariate analysis, those who selected the “other” option for possible benefits of PGD compared with those who selected from several predetermined options (e.g., having children without genetic mutations) and those who considered PGD in the context of
religion (as opposed to health and safety) were less likely to report that they would ever consider using PGD.

Cultural/Community Effects

The recognition that BRCA1/BRCA2 mutations are prevalent, not only in
breast/ovarian cancer families but also in some ethnic groups,[192] has led to
considerable discussion of the ethical, psychological, and other implications of
having one’s ethnicity be a factor in determination of disease predisposition.
Concerns that people will think everything is solely determined by genetic factors and the creation of a genetic underclass [193]
have been voiced. Questions about the impact on the group of being singled out
as having genetic vulnerability to breast cancer have been raised. There is
also confusion about who gives or withholds permission for the group to be
involved in studies of their genetic identity. These issues challenge
traditional views on informed consent as a function of individual autonomy.[194]

A growing literature on the unique factors influencing a variety of cultural subgroups suggests the importance of developing culturally specific genetic counseling and educational approaches.[95,195-199] The inclusion of members within the community of interest (e.g., breast cancer survivors, advocates, and community leaders) may enhance the development of culturally tailored genetic counseling materials.[96] One study showed that participation in any genetic counseling (culturally mediated or standard approaches) reduced perceived risk of developing breast cancer.[200]

Ethical Concerns

The human implications of the ethical issues raised by the advent of genetic
testing for breast/ovarian cancer susceptibility are described in case studies,[201] essays,[104,202] and research reports. Issues about rights and
responsibilities in families concerning the spread of information about genetic
risk promise to be major ethical and legal dilemmas in the coming decades.

Studies have shown that 62% of studied family members were aware of the family
history and that 88% of hereditary breast/ovarian cancer family members
surveyed have significant concerns about privacy and confidentiality.
Expressed concern about cancer in third-degree relatives, or relatives farther
removed, was about the same as that for first- or second-degree relatives of
the proband.[203] Only half of surveyed first-degree relatives of women with
breast or ovarian cancer felt that written permission should be required to
disclose BRCA1/BRCA2 test results to a spouse or immediate family member.
Attitudes toward testing varied by ethnicity, previous exposure to genetic
information, age, optimism, and information style. Altruism is a factor
motivating genetic testing in some people.[204] Many
professional groups have made recommendations regarding informed
consent.[108,204-207] There is some evidence that not all practitioners are
aware of or follow these guidelines.[208] Research shows that many BRCA1/BRCA2
genetic testing consent forms do not fulfill recommendations by professional
groups about the 11 areas that should be addressed,[209] and they omit highly
relevant points of information.[208] In a study of women with a history of breast or ovarian cancer, the interviews yielded that the women reported feeling inadequately prepared for the ethical dilemmas they encountered when imparting genetic information to family members.[210] These data suggest that more preparation about disclosure to family members before testing reduces the emotional burden of disseminating genetic information to family members. Patients and health care providers would benefit from enhanced consideration of the ethical issues of warning family members about hereditary cancer risk. (Refer to the PDQ summaries Cancer Genetics Risk Assessment and Counseling and Cancer Genetics Overview for more information about the ethics of cancer genetics and genetic testing.)

There is a small but growing body of literature on the use of decision aids as an adjunct to standard genetic counseling to assist patients in making informed decisions about cancer risk management.[211-214] One study showed that the use of a decision aid consisting of individualized value assessment and cancer risk management information after receiving positive BRCA1/BRCA2 test results was associated with fewer intrusive thoughts and lower levels of depression at the 6-month follow-up in unaffected women. Use of the decision aid did not alter cancer risk management intentions and behaviors. Slightly detrimental effects on well-being and several decision-related outcomes, however, were noted among affected women.[213]
Another study compared responses to a tailored decision aid (including a values-clarification exercise) versus a general information pamphlet intended for women making decisions about ovarian cancer risk management. In the short term, the women receiving the tailored decision aid showed a decrease in decisional conflict and increased knowledge compared with women receiving the pamphlet, but no differences in decisional outcomes were found between the two groups. In addition, the decision aid did not appear to alter the participant’s baseline cancer risk management decisions.[212] A third decision aid focused on breast cancer risk management decision support for women with a BRCA1/BRCA2 mutation. Pre-evaluations and postevaluations of the decision aid in 20 women showed that use of the aid resulted in a significant decrease in decisional conflict, improvement in knowledge, and a decrease in uncertainty about tamoxifen use, RRM and RRSO. No significant differences were identified in cancer-related distress after the use of the tool.[211]

Uptake of cancer risk management options

An increasing number of studies have examined uptake and adherence to cancer risk management options among individuals who have undergone genetic counseling and testing for BRCA1 and BRCA2 gene mutations. Findings from these studies are reported in Table 14 and Table 15. Outcomes vary across studies and include uptake or adherence to screening (mammography, magnetic resonance imaging [MRI], cancer antigen [CA] 125, transvaginal ultrasound [TVUS]) and selection of RRM and RRSO. Studies generally report outcomes by mutation carrier or testing status (e.g., mutation-positive, mutation-negative, or declined genetic testing). Follow-up time after notification of genetic risk status also varied across studies, ranging from 12 months up to several years.

Findings from these studies suggest that breast screening often improves after notification of BRCA1/BRCA2 mutation carrier status; nonetheless, screening remains suboptimal. Fewer studies have examined adoption of MRI as a screening modality, probably due to the recent availability of efficacy data. Screening for ovarian cancer varied widely across studies, and also varied based on type of screening test (i.e., CA-125 serum testing vs. TVUS screening). However, ovarian cancer screening does not appear to be widely adopted by BRCA1/BRCA2 mutation carriers. Uptake of RRM varied widely across studies, and may be influenced by personal factors (such as younger age or having a family history of breast cancer), psychosocial factors (such as a desire for reduction of cancer-related distress), recommendations of the health care provider, and cultural or health care system factors. An individual’s choice to have a bilateral mastectomy also appears to be influenced by pretreatment genetic education and counseling regardless of the genetic test results.[215] Similarly, uptake of RRSO also varied across studies, and may be influenced by similar factors, including older age, personal history of breast cancer, perceived risk of ovarian cancer, cultural factors (i.e., country), and the recommendations of the health care provider.

Predictors of RRSO and screening included being a BRCA mutation carrier, age 40–49 y, having a higher income, ≥2 children, a personal history of breast cancer, and a first-degree relative with ovarian cancer.

Uptake of RRSO was lower in women >60 y (22% uptake at 5 y). None of the women >70 y had a RRSO performed.

– 54.5%

BRCA2 carriers:

– BRCA1:
Mean, 2.29; range, 0.1–11.45 y

– 45.5%

All carriers with no personal history of breast cancer

– BRCA2:
Mean, 1.77; range, 0.1–11.1 y

Not affected with breast cancer

– 54.2%

All carriers with personal history of breast cancer

– BRCA1:
Mean, 1.63; range, 0.1–11.28 y

– 43.2%

– BRCA2:
Mean, 1.75; range, 0.1–8.98 y

On the other hand, many women found to be mutation carriers express interest in RRM in hopes of minimizing their risk of breast cancer. In one study of a number of unaffected women with no previous risk-reducing surgery who received results of BRCA1 testing after genetic counseling, 17% of carriers (2 of 12) intended to have mastectomies and 33% (4 of 12) intended to have oophorectomies.[115] In a later study of the same population, RRM was considered an important option by 35% of women who tested positive, whereas risk-reducing oophorectomy was considered an important option by 76%. A prospective study assessed the stability of risk management preferences over five time points (pre-BRCA testing to 9 months after results disclosure) among 80 Dutch women with a documented BRCA mutation. Forty-six participants indicated a preference for screening at baseline. Of 25 women who preferred RRM at baseline, 22 indicated the same preference 9 months after test results disclosure; however, it was not reported how many women actually had RRM.[231]

Initial interest does not always translate into the decision for surgery. Two different studies found low rates of RRM among mutation carriers in the year after result disclosure, one showing 3% (1 of 29) of carriers and the other 9% (3 of 34) of carriers having had this surgery.[169,232] Among members from a large BRCA1 kindred, utilization of cancer
screening and/or risk-reducing surgeries was assessed at baseline (before disclosure of results), and at 1 year and 2 years after disclosure of BRCA1 test results. Of the 269 men and women who participated, complete data were obtained on 37 female carriers and 92 female
noncarriers, all aged 25 years or older. At 2 years after disclosure of test results, none of the women had undergone RRM, although 4 of the 37 carriers (10.8%) said they were considering the procedure. In contrast, of the 26 women who had not had an oophorectomy before baseline, 46% (12 of 26) had obtained an oophorectomy by 2 years after testing. Of those carriers aged 25 to 39 years, 29% (5 of 17) underwent oophorectomy, while 78% (7 of 9) of the carriers aged 40 years and older had this procedure.[216] In a study assessing uptake of risk-reducing surgery 3 months after BRCA result disclosure, 7 of 62 women had undergone RRM and 13 of 62 women had undergone RRSO. Intent to undergo RRSO before testing correlated with procedure uptake. In contrast, intent to undergo RRM did not correlate with uptake. Overall, reasons given for indecision about risk-reducing surgery included complex testing factors such as the significance of family history in the absence of a mutation, concerns over the surgical procedure, and time and uncertainty regarding early menopause and the use of HRT.[233] In a UK study, data were collected during observations of genetic consultations and in semistructured interviews with 41 women after they received genetic counseling.[234] The option of risk-reducing surgery was raised in 29 consultations and discussed in 35 of the postclinic interviews. Fifteen women said they would consider having an oophorectomy in the future, and nine said they would consider having a mastectomy. The implications of undergoing oophorectomy and mastectomy were discussed in postclinic interviews. Risk-reducing surgery was described by the counselees as providing individuals with a means to (a) fulfill their obligations to other family members and (b) reduce risk and contain their fear of cancer. The costs of this form of risk management were described by the respondents as follows:

A number of women choose to undergo RRM and RRSO without genetic testing because of the following:

Testing is not readily accessible.

They do not wish exposure to the psychosocial risks of genetic testing.

They do not trust that a negative genetic test result means they are not at increased risk.

They find any level of risk, even baseline population risk, unacceptable.[235,236]

Among first-degree relatives of breast cancer patients attending a surveillance clinic, women who expressed an interest in RRM and/or had undergone surgery were found to
have significantly more breast cancer biopsies (P < .05) and higher subjective 10-year breast cancer risk estimates (P < .05) than women not interested in RRM. Cancer worry at the time of entry into the clinic was highest among women who subsequently underwent RRM compared with women who expressed interest but had not yet had surgery and women who did not intend to have surgery (P < .001).[237]

Few studies have evaluated the impact of BRCA1/BRCA2 test results on risk-reducing surgery decisions among women affected with breast cancer. A study that evaluated predictors of contralateral RRM among 435 breast cancer survivors found that 16% had undergone contralateral RRM (in conjunction with mastectomy of the affected breast) before referral for genetic counseling and BRCA1/BRCA2 genetic testing.[238] Predictors of contralateral RRM before genetic counseling and testing included younger age at breast cancer diagnosis, more time since diagnosis, having at least one affected first-degree relative, and not being employed full-time. In the year after disclosure of test results, 18% of women who tested positive for a BRCA1/BRCA2 mutation and 2% of those whose test results were uninformative underwent contralateral RRM. Predictors of contralateral RRM after genetic testing included younger age at breast cancer diagnosis, higher cancer-specific distress before genetic counseling, and having a positive BRCA1/BRCA2 test result. In this study, contralateral RRM was not associated with distress at 1 year after disclosure of genetic test results. A retrospective chart review evaluated uptake of bilateral mastectomies in 110 women who underwent BRCA1/BRCA2 genetic testing before making surgical decisions about the treatment of newly diagnosed breast cancer. BRCA mutation carriers were more likely to undergo bilateral mastectomies than were women in whom no mutation was detected (83% vs. 37%; P = .046).[239] The only predictor of contralateral RRM in women without a mutation was being married (P = .03). Age, race, parity, disease stage and biomarkers, increased mammographic breast density, and breast MRI did not influence contralateral RRM decisions at the time of primary surgical treatment.

Dutch women (N = 114) who had undergone unilateral or bilateral RRM with breast reconstruction between 1994 and 2002 were retrospectively surveyed to determine their satisfaction with the procedure.[240] Sixty-eight percent were either unaffected BRCA mutation carriers or at 50% risk of having a BRCA mutation in
their family. Sixty percent of respondents indicated that they were satisfied with the procedure, 95% would opt for RRM again, and 80% would opt for the same reconstruction procedure. Less than half reported some perioperative or postoperative complications, ongoing physical complaints, or some physical limitations. Twenty-nine percent reported altered feelings of femininity after the procedure, 44% reported adverse changes in their sexual relationships, and 35% indicated that they believed their partners experienced adverse changes in their sexual relationship. Ten percent of women, however, reported positive changes in their sexual relationship after the procedure. Compared with patients who indicated satisfaction with this procedure, nonsatisfied patients were more likely to feel less informed about the procedure and its consequences, report more complications and physical complaints, feel that their breasts did not belong to their body, and indicate that they would not opt for reconstruction again. Those who reported a negative effect on their sexual relationship were more likely to:

Feel less informed.

Experience more physical complaints and limitations.

Express that their breasts did not feel like their own.

Be disinclined to opt for reconstruction again.

State that the surgery had not met their expectations.

Experience altered feelings of femininity and perceived adverse changes in their partner’s view of their femininity and their sexual relationship.

Ninety Swedish women who had undergone RRM between 1997 and 2005 were surveyed before surgery, 6 months after surgery, and 1 year after surgery to evaluate changes in health-related quality of life, depression, anxiety, sexuality, and body image. There were no significant changes in health-related quality of life or depression at the three time points; anxiety decreased over time (P = .0004). More than 80% of women reported having an intimate relationship at all three time points. Women who reported being sexually active were asked to respond to questions about sexual pleasure, discomfort, habit, and frequency of activity. There were no statistically significant differences related to frequency, habit, or discomfort. However, pleasure significantly decreased between baseline and 1 year after surgery (P = .005). At 1 year after surgery, 48% of women reported feeling less attractive, 48% reported feeling self-conscious, and 44% reported dissatisfaction with surgical scars.[241]

Discussion of risk-reducing surgical options may not consistently occur during pretest genetic counseling. In one multi-institutional study, only one-half of genetics specialists discussed RRM and RRSO in consultations with women from high-risk breast cancer families,[242,243] despite the fact that discussion of surgical options was significantly associated with meeting counselees’ expectations, and that such information was not associated with increased anxiety.[244]

Given the increased risk of ovarian cancer faced by women with a BRCA1 or BRCA2 mutation, those who do receive information about RRSO show wide variations in surgery uptake (27%–72%).[19,121,225,228,245,246] A study showed that clinical factors related to choosing RRSO versus surveillance alone are older age, parity of one or more, and a prior breast cancer diagnosis.[247] In this study, the choice of RRSO was not related to family history of breast or ovarian cancer. Hysterectomy was presented as an option during genetic counseling and 80% of women who underwent RRSO also elected to have a hysterectomy.

Cancer screening and risk-reducing behaviors

Data are now emerging regarding uptake and adherence to cancer risk management recommendations such as screening and risk-reducing interventions. Cancer screening adherence and risk-reduction behaviors as defined by the NCCN Guidelines were assessed in a cross-sectional study of 214 women with a personal history (n = 134) or family history (n = 80) of breast or ovarian cancer. Among unaffected women older than 40 years, 10% had not had a mammogram or clinical breast examination (CBE) in the previous year and 46% did not practice breast self-examination (BSE). Among women previously affected with breast or ovarian cancer, 21% had not had a mammogram, 32% had not had a CBE, and 39% did not practice BSE.[248]

Three hundred and twelve women who were counseled and tested for BRCA mutations between 1997 and 2005 responded to a survey regarding their perception of genetic testing for hereditary breast and ovarian cancer. The survey included questions on risk reduction options, including screening and risk-reducing surgeries. Two hundred and seventeen (70%) of the women had been diagnosed with breast cancer, and 86 (28%) tested positive for a deleterious mutation in either the BRCA1 or BRCA2 gene. None of the BRCA-positive women agreed that mammograms are difficult procedures because of the discomfort, while 11 (5.4%) of the BRCA-negative women did agree with this statement. Both groups (BRCA-positive and BRCA-negative) agreed that risk-reducing surgeries provide the best means for lowering cancer risk and worry, and most patients in both groups expressed the belief that risk-reducing mastectomy is not too drastic, too scary, or too disfiguring.[249]

A prospective study from the United Kingdom examined the psychological impact of mammographic screening in 1,286 women aged 35 to 49 years who have a family history of breast cancer and were participants in a multicenter screening program. Mammographic abnormalities that required additional evaluation were detected in 112 women. These women, however, did not show a statistically significant increase in cancer worry or negative psychological consequences as a result of these findings. The 1,174 women who had no mammographic abnormality detected experienced a decrease in cancer worry and a decrease in negative psychological consequences compared with baseline after receipt of their results. At 6 months, the entire cohort had experienced a decrease in measures of cancer worry and psychological consequences of breast screening.[250]

A qualitative study explored health care professionals’ views regarding the provision of information about health protective behaviors (e.g., exercise and diet). Seven medical specialists and ten genetic counselors were interviewed during a focus group or individually. The study reported wide variation in the content and extent of information provided about health-protective behaviors and in general, participants did not consider it their role to promote such behaviors in the context of a genetic counseling session. There was agreement, however, about the need to form consensus about provision of such information both within and across risk assessment clinics.[251]

Not all studies specify whether screening uptake rates fall within recommended guidelines for the targeted population or the specific clinical scenario, nor do they report on other variables that may influence cancer screening recommendations. For example, women who have a history of atypical ductal hyperplasia would be advised to follow screening recommendations that may differ from those of the general population.

Psychosocial Outcome Studies

Risk-reducing mastectomy

A prospective study conducted in the Netherlands found that among 26 BRCA1/BRCA2 mutation carriers, the 14 women who chose mastectomy had higher distress both before test result disclosure and 6 and 12 months later, compared with the 12 carriers who chose surveillance and compared with 53 non–mutation carriers. Overall, however, anxiety declined in women undergoing prophylactic mastectomy; at 1 year, their anxiety scores were closer to those of women choosing surveillance and to the scores of non–mutation carriers.[252] Interestingly, women opting for prophylactic mastectomy had lower pretest satisfaction with their breasts and general body image than carriers who opted for surveillance or noncarriers of BRCA1/BRCA2 mutations. Of the women who had a prophylactic mastectomy, all but one did not regret the decision at 1 year posttest disclosure, but many had difficulties with body image, sexual interest and functioning, and self-esteem. The perception that doctors had inadequately informed them about the consequences of prophylactic mastectomy was associated with regret.[252] At 5-year follow-up, women who had undergone RRM had less favorable body image and changes in sexual relationships, but also had a significant reduction in the fear of developing cancer.[123] In a study of 78 women who underwent risk-reducing surgery (including BRCA1/BRCA2 carriers and women who were from high-risk families with no detectable BRCA1/BRCA2 mutation), cancer-specific and general distress were assessed 2 weeks before surgery and at 6 and 12 months postsurgery.[253] The sample included women who had RRM and RRSO alone and women who had both surgeries. There was no observable increase in distress over the 1-year period.

Mixed psychosocial outcomes were reported in a follow-up study (mean 14 years) of 609 women who received prophylactic mastectomies at the Mayo Clinic. Seventy percent were satisfied with prophylactic mastectomy, 11% were neutral, and 19% were dissatisfied. Eighteen percent believed that if they had the choice to make again, they probably or definitely would not have a prophylactic mastectomy. About three quarters said their worry about cancer was diminished by surgery. One-half reported no change in their satisfaction with body image; 16% reported improved body image after surgery. Thirty-six percent said they were dissatisfied with their body image after prophylactic mastectomy. About one-quarter of the women reported adverse impact of prophylactic mastectomy on their sexual relationships and sense of femininity, and 18% had diminished self-esteem. Factors most strongly associated with satisfaction with prophylactic mastectomy were postsurgical satisfaction with appearance, reduced stress, no reconstruction or lack of problems with implants, and no change or improvement in sexual relationships. Women who cited physician advice as the primary reason for choosing prophylactic mastectomy tended to be dissatisfied after prophylactic mastectomy.[254]

A study of 60 healthy women who underwent RRM measured levels of satisfaction, body image, sexual functioning, intrusion and avoidance, and current psychological status at a mean of 4 years and 4 months postsurgery. Of this group, 76.7% had either a strong family history (21.7%) or carried a BRCA1 or BRCA2 mutation (55%). Overall, 97% of the women surveyed were either satisfied (17%) or extremely satisfied (80%) with their decision to have RRM, and all but one participant would recommend this procedure to other women. Most women (66.7%) reported that surgery had no impact on their sexual life, although 31.7% reported a worsening sexual life, and 76.6% reported either no change in body image or an improvement in body image, regardless of whether reconstruction was performed. Worsening self-image was reported by 23.3% of women after surgery. Women’s mean distress levels after surgery were only slightly above normal levels, although those women who continued to perceive their postsurgery breast cancer risk as high had higher mean levels of global and cancer-related distress than those who perceived their risk as low. Additionally, BRCA1 and BRCA2 mutation carriers and women with a strong family history of breast and/or ovarian cancer had higher mean levels of cancer-related distress than women with a limited family history.[255]

Very little is known about how the results of genetic testing affect treatment decisions at the time of cancer diagnosis. Two studies explored genetic counseling and BRCA1/BRCA2 genetic testing at the time of breast cancer diagnosis.[215,256] One of these studies found that genetic testing at the time of diagnosis significantly altered surgical decision making, with more mutation carriers than noncarriers opting for bilateral mastectomy. Bilateral RRM was chosen by 48% of mutation-positive women [215] and by 100% of mutation-positive women in a smaller series [256] of women undergoing testing at the time of diagnosis. Of women in whom no mutation was found, 24% also opted for bilateral RRM. Four percent of the test decliners also underwent bilateral RRM. Among mutation carriers, predictors of bilateral RRM included whether patients reported that their physicians had recommended BRCA1/BRCA2 testing and bilateral RRM before testing, and whether they received a positive test result.[215] Data are lacking on quality-of-life outcomes for women who undergo RRM after genetic testing that is performed at the time of diagnosis.

A prospective study from the Netherlands evaluated long-term psychological outcomes of offering women with breast cancer genetic counseling and, if indicated, genetic testing at the onset of breast radiation for treatment of their primary breast cancer. Of those who were approached for counseling, some underwent genetic testing and chose to receive their result (n = 58), some were approached but did not fulfill referral criteria (n = 118), and some declined the option of counseling/testing (n = 44). Another subset of women undergoing radiation therapy was not approached for counseling (n = 182) but was followed using the same measures. Psychological distress was measured at baseline and at 4, 11, 27, and 43 weeks after initial consultation for radiation therapy. No differences were detected in general anxiety, depression or breast cancer–specific distress across all four groups.[257]

A retrospective questionnaire study of 583 women with a personal and family history of breast cancer and who underwent contralateral prophylactic mastectomy between 1960 and 1993 measured overall satisfaction after mastectomy and factors influencing satisfaction and dissatisfaction with this procedure.[258] The mean time of follow-up was 10.3 years after prophylactic surgery. Overall, 83% of all participants stated they were satisfied or very satisfied, 8% were neutral, and 9% were dissatisfied with contralateral prophylactic mastectomy. Most women also reported favorable effects or no change in their self-esteem, level of stress, and emotional stability after surgery (88%, 83%, and 88%, respectively). Despite the high levels of overall satisfaction, 33% reported negative body image, 26% reported a reduced sense of femininity, and 23% reported a negative effect on sexual relationships. The type of surgical procedure also affected levels of satisfaction. The authors attributed this difference to the high rate of unanticipated reoperations in the group of women having subcutaneous mastectomy (43%) versus the group having simple mastectomy (15%) (P < .0001). Limitations to this study are mostly related to the time period during which participants had their surgery (i.e., availability of surgical reconstructive option).[258,259] None of these women had genetic testing for mutations in the BRCA1/BRCA2 genes. Nevertheless, this study shows that while most women in this group were satisfied with contralateral prophylactic mastectomy, all women reported at least one adverse outcome.

Another study compared long-term quality-of-life outcomes in 195 women after bilateral RRM performed between 1979 and 1999 versus 117 women at high risk of breast cancer opting for screening. No statistically significant differences were detected between the groups for psychosocial outcomes. Eighty-four percent of those opting for surgery reported satisfaction with their decision. Sixty-one percent of women from both the surgery and screening groups reported being very much or quite a bit contented with their quality of life.[260]

In a study of psychosocial outcomes associated with RRM and immediate reconstruction, 61 high-risk women (27 mutation carriers, others with high-risk family history), 31 of whom had a prior history of breast cancer, were evaluated on average 3 to 4 years after surgery.[261] The study utilized questions designed to elicit yes versus no responses and found that the surgery was well-tolerated with 83% of
participants reporting that the results of their reconstructive surgery were as they expected, 90% reporting that they had received adequate preoperative information, none reporting that they regretted the surgery, and all reporting that
they would choose the same
route if they had to do it again. Satisfaction with the results ranged from 74% satisfied with the shape of their breasts to 89% satisfied with the appearance of the scarring. Comparison of this group to normative samples on quality-of-life indicators (Short Form 36 Health Survey Questionnaire [SF-36]; Hospital Anxiety and Depression Scale questionnaire scores) indicated no reductions in quality of life in these women.

A qualitative study examining material on the FORCE Web site posted by 21 high-risk women (BRCA1/BRCA2 positive) undergoing RRM showed that these women anticipated and received negative reactions from friends and family regarding the surgery, and that they managed disclosure in ways to maintain emotional support and self-protection for their decision. Many of the women expressed a relief from intrusive breast cancer thoughts and worry, and were satisfied with the cosmetic result of their surgery.[262]

In contrast, another study examined long-term psychosocial outcomes in 684 women who had had bilateral or contralateral RRM on average 9 years before assessment.[263] A majority of women (59%) also had reconstructive surgery. Interestingly, based on a Likert scale, 85% of women reported that they were satisfied or very satisfied with their decision to have an RRM. However, in qualitative interviews, a large number of women went on to describe dissatisfaction or negative psychosocial outcomes associated with surgery. The authors coded the responses as negative when women reported still being anxious about their breast cancer risk and/or reported negative feelings about their body image, pain, and sexuality. Seventy-nine percent of the women providing negative comments and 84% of those making mixed comments (mixture of satisfaction and dissatisfaction) responded that they were either satisfied or very satisfied with their decision. Twice as many women with bilateral mastectomy made negative and mixed comments than did women with contralateral mastectomy. The areas of most concern were body image, problems with breast implants, pain after surgery, and sexuality. The authors proposed that those who had undergone contralateral procedures had already been treated for cancer, while those who had undergone bilateral procedures had not been treated previously, and this may partially account for the differences in satisfaction between the two groups. These findings suggest that women's satisfaction with RRM may be tempered by their complex reactions over time.

In a qualitative study of 108 women who underwent or were considering RRM, more than half of those who had RRM felt that presurgical consultation with a psychologist was advisable; nearly two-thirds thought that postsurgical consultation was also appropriate. All of the women who were considering RRM believed that psychological consultation before surgery would facilitate decision-making.[264]

Risk-reducing salpingo-oophorectomy

A retrospective self-administered survey of 40 women aged 35 to 74 years at time of RRSO (57.5% were younger than 50 years), who had undergone the procedure through the Ontario Ministry of Health due to a family history of ovarian cancer, found that RRSO resulted in a significant reduction in perceived ovarian cancer risk. Fifty-seven percent identified a
decrease in perceived risk as a benefit of RRSO (35% did not comment on RRSO benefits) and 49% reported that they would repeat RRSO to decrease cancer risk. The overall quality-of-life scores were consistent with those published for women who are menopausal or participating in hormone studies.[265] Quality of life in 59 women who underwent RRSO was assessed at 24 months postprocedure.[266] Overall quality of life was similar to the general population and breast cancer survivors, with approximately 20% reporting depression. The 30% of subjects reporting vaginal dryness and dyspareunia were more likely to report dissatisfaction with the procedure.

A Canadian prospective study examined the impact of RRSO on menopausal symptoms and sexual functioning before surgery and then 1 year later in a sample of 114 women with known BRCA1/2 mutations.[267] Satisfaction with the decision to undergo RRSO was high regardless of symptoms reported. Those who were premenopausal at the time of surgery (n = 75) experienced a worsening of symptoms and a decline in sexual functioning. HRT addressed vaginal dryness and dyspareunia but not declines in sexual pleasure. HRT also resulted in fewer moderate to severe hot flashes.

Additional work reported by this group found that the majority of the 127 women who had undergone RRSO 1 year previously (75 with BRCA1 mutations; 52 with BRCA2 mutations) felt that RRSO reduced their risk of both breast and ovarian cancer.[268] There was a wide range of risk perceptions for ovarian cancer noted in the group. Twenty percent of BRCA1 and BRCA2 mutation carriers thought that their risk of ovarian cancer was completely eliminated; others had an inflated perception of their ovarian cancer risk both before and after surgery. A small group of these women were further surveyed at about 3 years postsurgery and their risk perceptions did not change significantly during this extended time period. These findings suggest that important misperceptions about ovarian cancer risk may persist after RRSO. Additional genetic education and counseling may be warranted.

A larger study assessed quality of life in women at high risk of ovarian cancer who opted for periodic gynecologic screening (GS) versus those who underwent RRSO. Eight hundred forty-six high-risk women, 44% of whom underwent RRSO and 56% of whom chose GS, completed questionnaires evaluating quality of life, cancer-specific distress, endocrine symptoms, and sexual functioning.[269] Women in the RRSO group were a mean of 2.8 ±1.9 years from surgery and women in the GS group were a mean of 4.3 years from their first visit to a gynecologist for high-risk management. No statistical difference in overall quality of life was detected between the RRSO and GS groups. When compared with the GS group, women who underwent RRSO had poorer sexual functioning and more endocrine symptoms such as vaginal dryness, dyspareunia, and hot flashes. Women who underwent RRSO experienced lower levels of breast and ovarian cancer distress and had a more favorable perception of cancer risk.

Women (N = 182) at risk of hereditary breast and ovarian cancer referred for genetic counseling were surveyed concerning their satisfaction with their choice of either RRSO or periodic screening (PS) (biannual pelvic examination with TVUS and CA-125 determination) to manage their ovarian cancer risk.[270] Overall satisfaction with both options was extremely high, but highest among those who chose RRSO over PS. There were no other demographic or clinical factors that distinguished satisfaction level. There was higher decisional ambivalence among those who chose PS.

A retrospective study assessed 98 BRCA mutation carriers who underwent RRSO about their preoperative counseling regarding symptoms to expect after surgery.[271] The mean age at RRSO was 45.5 years (range, ages 32–63 years). Eighty-five percent pursued RRSO after learning that they harbored a BRCA mutation, and 48.0% were premenopausal at the time of surgery. Participants reported ‘‘frequent’’ or ‘‘very frequent’’ postsurgical symptoms of vaginal dryness (52.1%), changes in interest in sex (50.0%), sleep disturbances (46.7%), changes in sex life (43.9%), and hot flashes (42.9%). Only vaginal dryness and hot flashes were commonly recalled to have been addressed preoperatively. While 96% would have the surgery again, participants reported that the discussion of the impact of surgery on their sex life (59.2%), risk of coronary heart disease (57.1%), and the availability of sex counseling (57.1%) would have been helpful.

Interventions: Psychological

Several psychological interventions have been proposed for women who may
have hereditary risk of breast cancer, but few of these have been rigorously
tested. Issues faced by these women include the following:

Confronting the meaning of one’s risk status and venting strong
feelings of fear of harm, disfigurement, pain, or death.

Addressing guilt about passing on genetic risk or not doing enough for
loved ones.

Psychotherapy for women interested in prophylactic mastectomy is discussed in one
report.[272] Another recommends rehearsal of affective state in the context of
all potential outcomes of cancer genetic testing for BRCA1/BRCA2.[273] As genetic
testing programs grow and the psychological outcomes and behavioral impact of
testing are further defined, there will be an increasing demand for
interventions to maximize the benefits of cancer genetic testing and minimize
the risks to carriers and family members.

A randomized trial with 126 BRCA1/BRCA2 mutation carriers evaluated whether psychological and behavioral outcomes of BRCA1/BRCA2 testing are improved among mutation carriers by providing a psychosocial telephone counseling intervention in addition to standard genetic counseling.[274] The intervention consisted of five 60- to 90-minute telephone counseling sessions. The first session was a semistructured clinical assessment interview designed to allow the mutation carrier to describe her experiences and reactions to BRCA testing results. The second through the fourth telephone sessions were individualized to the concerns raised by the woman in the domains of making medical decisions, managing family concerns, and emotional reactions after the receipt of a positive BRCA1/BRCA2 result. The final telephone session focused on integration and closure on the issues raised and implementation of a plan for short-term and long-term goals established during the telephone intervention. Women most likely to complete the intervention were those who did not have a personal history of cancer; those who had higher levels of cancer-specific distress; those who were college graduates; and those who were employed. Outcome data from this study has not yet been reported.

A pilot study demonstrated the usefulness of a six-session psychoeducational
support group for women at high genetic risk of breast cancer who were
considering prophylactic mastectomy. The themes for the group sessions
included overestimation of and anxiety about risk, desire for hard data,
emotional impact of watching a mother die of breast cancer, concerns about
spouse reactions, self-image and body image, the decision-making process, and
confusion about whom to trust in decision-making. Both the participants and the
multidisciplinary leaders concluded that as a supplement to individual
counseling, a support group is a beneficial and cost-effective treatment
modality.[275]

A prospective study from the Netherlands [276] involving 163 newly-identified BRCA mutation carriers with no history of cancer considered the effects of psychoeducational support sessions on completion of intended risk management preferences (breast cancer surveillance or prophylactic mastectomy). All were offered the opportunity to participate in eight sessions focused on psychosocial (five sessions) and medical information (three sessions) after the receipt of test results. The number of women with a preference for mastectomy after receipt of test results who actually had a mastectomy at follow-up (median 2 years) was higher in the group that attended the psychoeducational support sessions than among those who did not attend (89% and 63%, respectively; OR, 4.8; P = .04).

Women who called the National Cancer Institute's Cancer Information Service seeking information about breast or ovarian cancer risk, risk assessment, or cancer genetic testing, were randomly assigned to receive (1) general information about cancer risk and a referral to testing and counseling services or (2) an educational intervention designed to increase knowledge and understanding about inherited cancer risk, personal history of cancer, and the benefits and limitations of genetic testing. In the group receiving the educational intervention, intention to obtain genetic testing decreased among women at average breast cancer risk (as determined by the Gail model) and increased among women at high risk. Among average risk women, those in the intervention group identified as high monitors (i.e., those who seek and pay greater attention to threatening health-related information) demonstrated an increase in knowledge and breast cancer risk perceptions compared with low monitors (i.e., those who avoid attending to threatening health-related information).[277]

Other minimally intensive interventions (e.g., leaflets) have been explored and show promise in reducing psychological distress while genetic testing results are pending and after risk disclosure.[278] Additional studies are needed to examine this type of intervention, which is more readily disseminated on a wider scale.

Behavioral Outcomes

A study [279] of screening behaviors of 216 self-referred, high-risk (>10% risk of carrying a BRCA1/BRCA2 mutation) women who are members of hereditary breast cancer families found a range of screening practices. Even the presence of known mutations in their families was not associated with good adherence to recommended screening practices. Sixty-nine percent of women aged 50 to 64 years and 83% of women aged 40 to 49 years had had a screening mammogram in the previous year. Twenty percent of participants had ever had a CA-125 test and 31% had ever had a pelvic ultrasound or TVUS. Further analysis of this study population [279] looking specifically at 107 women with informative BRCA test results found good use of breast cancer screening, though the uptake rate in younger carriers is lower. The reason for the lower uptake rate was not explored in this study.[280] One survey of screening behaviors among women at increased risk of breast/ovarian cancer identified physician recommendations as a significant factor in adherence to screening.[281]

While motivations cited for pursuing genetic testing often include the expectation that mutation carriers will be more compliant with breast and/or ovarian screening recommendations,[279,282-284] limited data exist about whether participants in genetic testing alter their screening behaviors over time and about other variables that may influence those behaviors, such as insurance coverage and physician recommendations or attitudes.
The impact of cancer genetic counseling on screening behaviors was assessed in a U.K. study of 293 women followed for 12 months postcounseling at four cancer genetics clinics.[285] BSE, CBE, and mammography were significantly increased after counseling; however, gaps in adherence to recommendations were noted: 38% of women aged 35 to 49 years had not had a mammogram by 12 months postcounseling. BSE was not done by most women at the recommended time and frequency.

This is a critical issue not only for women testing positive, but also for
adherence to screening for those testing negative and those who have
received indeterminate results or choose not to receive their results. It is
possible that adherence actually diminishes with a decrease in the perceived
risk that may result from a negative genetic test result.

In addition, while there is still some question regarding the link between
cancer-related worry and breast cancer screening behavior, accumulating
evidence appears to support a linear rather than a curvilinear relationship.
That is, for some time, the data were not consistent; some data supported the
hypothesis that mild-to-moderate worry may increase adherence, while excessive
worry may actually decrease the utilization of recommended screening practices.
Other reports support the notion that a linear relationship is more likely;
that is, more worry increases adherence to screening recommendations. Few
studies, however, have followed women to assess their health behaviors
after genetic testing. Thus, a negative test result leading to decreased
worry could theoretically result in decreased screening adherence. A large study found that patient compliance with screening practices was not related to general or screening-specific anxiety—with the exception of BSE, for which compliance is negatively associated with procedure-specific anxiety.[75] Further
research designed to clarify this potential concern would highlight the need
for comprehensive genetic counseling to discuss the need for follow-up
screening.

Further complicating this area of research are issues such as the baseline rate
of mammography adherence among women older than 40 or 50 years before genetic
testing. More specifically, the ability to note a significant difference in
adherence on this measure may be affected by the high adherence rate to this
screening behavior before genetic testing by women undergoing such testing. It
may be easier to find significant changes in mammography use among women with a
family history of breast cancer who test positive. Finally, adherence over
time will likely be affected by how women undergoing genetic
testing and their caregivers perceive the efficacy of many of the screening options
in question, such as mammography for younger women, BSE,
and ovarian cancer screening (periodic vaginal ultrasound and serum CA-125
measurements), along with the value of preventive interventions.

The issue of screening decision-making and adherence among women undergoing
genetic testing for breast and ovarian cancer is the subject of several ongoing
trials, and an area of much needed ongoing study.

Dabney MK, Huelsman K: Counseling by computer: breast cancer risk and genetic testing. Developed by the University of Wisconsin-Madison Department of Medicine and the Program in Medical Ethics. Genet Test 4 (1): 43-4, 2000. [PUBMED Abstract]

Macke E: A family history of breast and ovarian cancer. In: Marteau T, Richards M, eds.: The Troubled Helix: Social and Psychological Implications of the New Human Genetics. Cambridge, England: Cambridge University Press, 1996, pp 31-37.

Kenen R, Arden-Jones A, Eeles R: We are talking, but are they listening? Communication patterns in families with a history of breast/ovarian cancer (HBOC). Psychooncology 13 (5): 335-45, 2004. [PUBMED Abstract]

Bradbury AR, Dignam JJ, Ibe CN, et al.: How often do BRCA mutation carriers tell their young children of the family's risk for cancer? A study of parental disclosure of BRCA mutations to minors and young adults. J Clin Oncol 25 (24): 3705-11, 2007. [PUBMED Abstract]

Vadaparampil ST, Quinn GP, Small BJ, et al.: A pilot study of hereditary breast and ovarian knowledge among a multiethnic group of Hispanic women with a personal or family history of cancer. Genet Test Mol Biomarkers 14 (1): 99-106, 2010. [PUBMED Abstract]